The objective of this study is to characterize the pathophysiological alterations induced by IgE antibody in respiratory and circulatory structure and/or function and to elucidate the mechanisms by which such alterations occur. The experimental design involves the utilization of a unique model system in which rabbits sensitized to a soluble protein antigen synthesize only IgE antibody to that antigen and upon intravenous challenge exhibit systemic anaphylaxis (SA). This systemic allergic reaction has been characterized with respect to alterations in eight variables in respiratory and circulatory function. We are examining this reaction to determine (a) whether IgE and antigen are the only essential components for initiation in an otherwise normal animal; (b) whether basophils or mast cells or both play a role in the response; (c) whether platelets are a requirement of the response; and (d) whether the response can be prevented by inhibiting the effects of the purported mediators of acute allergic reactions. To date we have shown that chlorpheniramine blocks the respiratory changes but not the circulatory alterations nor the lethality of IgE-induced SA. Also, mast-cell-bound IgE in the absence of basophil-bound IgE is sufficient to initiate SA. Studies of the response to aerosol antigen challenge have been negative to date with respect to any detectable alterations in the variables monitored. Other future studies include a direct demonstration of the site of IgE-induced airway alteration(s) through the use of the microfocal spot technique and determination of any chronic alterations occuring as a result of repeated antigen challenge over several months.